Variant 11-18296152-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_181507.2(HPS5):c.1511-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,603,210 control chromosomes in the GnomAD database, including 295,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26485 hom., cov: 32)

Exomes 𝑓: 0.61 ( 268522 hom. )

Consequence

HPS5
NM_181507.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.152

Variant links:

Genes affected

HPS5 (HGNC:17022): (HPS5 biogenesis of lysosomal organelles complex 2 subunit 2) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. This protein interacts with Hermansky-Pudlak syndrome 6 protein and may interact with the cytoplasmic domain of integrin, alpha-3. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 5. Multiple transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

HPS5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 11-18296152-C-T is Benign according to our data. Variant chr11-18296152-C-T is described in ClinVar as [Benign]. Clinvar id is 262983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPS5	NM_181507.2 linkuse as main transcript	c.1511-30G>A		intron_variant		ENST00000349215.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
HPS5	ENST00000349215.8 linkuse as main transcript	c.1511-30G>A	intron_variant	1	NM_181507.2	P1	Q9UPZ3-1
HPS5	ENST00000396253.7 linkuse as main transcript	c.1169-30G>A	intron_variant	1			Q9UPZ3-2
HPS5	ENST00000438420.6 linkuse as main transcript	c.1169-30G>A	intron_variant	1			Q9UPZ3-2
HPS5	ENST00000531848.1 linkuse as main transcript		downstream_gene_variant	5

Frequencies

GnomAD3 genomes

AF:

0.587

AC:

89117

AN:

151844

Hom.:

26449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.573

Gnomad AMI

AF:

0.709

Gnomad AMR

AF:

0.589

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.849

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.585

Gnomad OTH

AF:

0.560

GnomAD3 exomes

AF:

0.594

AC:

148002

AN:

249122

Hom.:

44916

AF XY:

0.590

AC XY:

79569

AN XY:

134758

show subpopulations

Gnomad AFR exome

AF:

0.572

Gnomad AMR exome

AF:

0.598

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.858

Gnomad SAS exome

AF:

0.601

Gnomad FIN exome

AF:

0.553

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.551

GnomAD4 exome

AF:

0.605

AC:

878169

AN:

1451248

Hom.:

268522

Cov.:

AF XY:

0.603

AC XY:

435357

AN XY:

722540

show subpopulations

Gnomad4 AFR exome

AF:

0.566

Gnomad4 AMR exome

AF:

0.597

Gnomad4 ASJ exome

AF:

0.460

Gnomad4 EAS exome

AF:

0.809

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.553

Gnomad4 NFE exome

AF:

0.608

Gnomad4 OTH exome

AF:

0.598

GnomAD4 genome

AF:

0.587

AC:

89206

AN:

151962

Hom.:

26485

Cov.:

AF XY:

0.587

AC XY:

43628

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.574

Gnomad4 AMR

AF:

0.589

Gnomad4 ASJ

AF:

0.467

Gnomad4 EAS

AF:

0.849

Gnomad4 SAS

AF:

0.621

Gnomad4 FIN

AF:

0.545

Gnomad4 NFE

AF:

0.585

Gnomad4 OTH

AF:

0.565

Alfa

AF:

0.479

Hom.:

2430

Bravo

AF:

0.592

Asia WGS

AF:

0.747

AC:

2592

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Hermansky-Pudlak syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.8

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over